A growing body of evidence suggests cognitive problems can occur as a consequence of systemic cancer treatment. Although progress has been made in understanding these problems, several important gaps remain. One notable gap is the lack of research on men with prostate cancer, the most common cancer in U.S. men. Concern rests primarily with the estimated 50,000 men per year who are candidates for treatment with luteinizing hormone- releasing hormone (LHRH) agonists. The concern reflects the fact that these agents act against prostate cancer by blocking testosterone production. In addition to giving rise to side effects that can interfere with cognitive functioning (e.g., fatigue, depression, and hot flashes), LHRH agonists may have a direct effect on cognitive functioning. Evidence for this includes studies showing that lower levels of testosterone are associated with poorer cognitive functioning in healthy older men and that testosterone supplementation in men is associated with improvements in cognitive functioning. Additional evidence includes a small number of studies showing problems with cognitive functioning among prostate cancer patients receiving LHRH agonists. Most of these studies, however, have been characterized by methodological limitations (i.e., small sample sizes, use of cross-sectional research designs, and absence of appropriate comparison groups). In addition, there has been little effort to examine mechanisms that may underlie the impact of LHRH agonists on cognitive functioning or to identify patient characteristics that may moderate their impact on cognitive functioning. With these issues in mind, the aims of the current study are: 1) to identify the magnitude and features of changes in cognitive functioning attributable to treatment of prostate cancer with LHRH agonist therapy;2) to examine the relationship of changes in testosterone and estradiol to changes in cognitive functioning during treatment with LHRH agonist therapy;3) to identify whether genetic variations associated with cognitive functioning in other populations are predictive of changes in cognitive functioning related to receipt of LHRH agonist therapy;and 4) to identify whether cognitive difficulties during LHRH agonist therapy are part of a cluster of symptoms related to declines in testosterone that also includes hot flashes, fatigue, depressive symptoms, and loss of sexual desire. These aims will be addressed through the study of men with prostate cancer receiving LHRH agonist therapy and matched comparison samples of men with prostate cancer not receiving LHRH agonist therapy and men with no history of cancer. Public Health Relevance Paragraph: By learning more about the cognitive problems experienced by men receiving hormonal therapy for prostate cancer, we hope to lay the groundwork for future efforts to improve the quality of life of these individuals. This aim is consistent with the strategic objective of improving the quality of life of cancer patients and survivors outlined in the National Cancer Institute's 2015 Challenge Goal of Eliminating the Suffering and Death Due to Cancer.